| Hirudin | |||||||||
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| Identifiers | |||||||||
| Symbol | Hirudin | ||||||||
| Pfam | PF00713 | ||||||||
| InterPro | IPR000429 | ||||||||
| SCOP2 | 4htc /SCOPe /SUPFAM | ||||||||
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Hirudin is a naturally occurringpeptide in thesalivary glands ofblood-suckingleeches (such asHirudo medicinalis) that has a bloodanticoagulant property.[2] This is essential for the leeches' habit offeeding on blood, since it keeps a host's blood flowing after the worm's initialpuncture of the skin.
Hirudin (MEROPS I14.001) belongs to a superfamily (MEROPS IM) ofprotease inhibitors that also includeshaemadin (MEROPS I14.002) andantistasin (MEROPS I15).[3][4]
During his years in Birmingham and Edinburgh,John Berry Haycraft had been actively engaged in research and published papers on the coagulation of blood, and in 1884, he discovered that the leech secreted a powerful anticoagulant, which he named hirudin, although it was not isolated until the 1950s, nor its structure fully determined until 1976. Full length hirudin is made up of 65 amino acids. These amino acids are organized into a compact N-terminal domain containing threedisulfide bonds and a C-terminal domain that is completely disordered when the protein isun-complexed in solution.[5][6]Amino acid residues 1-3 form a parallel beta-strand with residues 214-217 ofthrombin, thenitrogenatom of residue 1 making ahydrogen bond with theSer-195 O gamma atom of thecatalytic site. The C-terminal domain makes numerouselectrostatic interactions with ananion-bindingexosite of thrombin, while the last five residues are in ahelicalloop that forms many hydrophobic contacts.[7] Natural hirudin contains a mixture of variousisoforms of the protein. However,recombinant techniques can be used to producehomogeneous preparations of hirudin.[8]
A key event in the final stages ofblood coagulation is the conversion offibrinogen intofibrin by theserine protease enzymethrombin.[9] Thrombin is produced fromprothrombin, by the action of an enzyme, prothrombinase (Factor Xa along with Factor Va as a cofactor), in the final states of coagulation. Fibrin is then cross linked by factor XIII (Fibrin Stabilizing Factor) to form ablood clot. The principalinhibitor ofthrombin in normal blood circulation isantithrombin.[8] Similar to antithrombin, the anticoagulant activity of hirudin is based on its ability to inhibit the procoagulant activity ofthrombin.
Hirudin is the most potent natural inhibitor of thrombin. Unlike antithrombin, hirudin binds to and inhibits only the activated thrombin, with a specific activity on fibrinogen.[8] Therefore, hirudin prevents or dissolves the formation of clots andthrombi (i.e., it has athrombolytic activity)[citation needed], and has therapeutic value inblood coagulation disorders, in the treatment ofskinhematomas and of superficialvaricose veins, either as an injectable or a topical application cream. In some aspects, hirudin has advantages over more commonly used anticoagulants and thrombolytics, such asheparin, as it does not interfere with the biological activity of otherserum proteins, and can also act oncomplexed thrombin.
| Hirudin variant-1 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Organism | Hirudo medicinalis | ||||||
| Symbol | ? | ||||||
| UniProt | P01050 | ||||||
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It is difficult to extract large amounts of hirudin from natural sources, so a method for producing and purifying this protein (specifically P01050 in the infobox) usingrecombinantbiotechnology has been developed. This has led to the development and marketing of a number of hirudin-based anticoagulant pharmaceutical products, including:
Several otherdirect thrombin inhibitors are derived chemically from hirudin.